Simultaneous Osteoperiosteal Autologous Iliac Crest Graft and Lateral Meniscus Allograft Transplantation for Osteochondral Lesion with Bony Defect and Lateral Discoid Meniscus Tear.
The optimal treatment for combined osteochondritis dissecans (OCD) with considerable bony defect of the lateral femoral condyle (LFC) and torn discoid lateral meniscus is unclear. We present a case of a 15-year-old female who was a gymnast and had a large OCD lesion in the LFC combined with deficiency of the lateral meniscus. The patient underwent the "one-step" technique of osteoperiosteal autologous iliac crest graft and lateral meniscus allograft transplantation after a failure of meniscectomy with repair at another hospital. Twenty-four months postoperatively, clinical results were significantly improved. Follow-up imaging tests and second-look arthroscopy showed well incorporated structured bone graft and fibrous cartilage regeneration as well as stabilized lateral meniscus allograft. She could return to her sport without any pain or swelling. This "one-step" surgical technique is worth considering as a joint salvage procedure for massive OCD lesions with torn discoid lateral meniscus.


Sad people are more accurate at expression identification with a smaller own-ethnicity bias than happy people.
Sad individuals are more accurate at face identity recognition, possibly because they scan more of the face during encoding. During expression identification tasks, sad individuals do not fixate on the eyes as much as happier individuals. Fixating on features other than the eyes leads to a reduced own-ethnicity bias. This background indicates that sad individuals would not view the eyes as much as happy individuals, and this would result in improved expression recognition and reduced own-ethnicity bias. This prediction was tested using an expression identification task with eye tracking. We demonstrate that sad-induced participants show enhanced expression recognition and a reduced own-ethnicity bias than happy-induced participants due to scanning more facial features. We conclude that mood affects eye movements and face encoding by causing a wider sampling strategy and deeper encoding of facial features diagnostic for expression identification.


[Hemolytic uremic syndrome caused by Shiga-toxin-producing Escherichia coli].
Every year in France, approximately one hundred children, aged from 6 months to 3 years, develop hemolytic uremic syndrome (HUS) secondary to Shiga toxin-producing Escherichia coli (STEC) infection, mostly the O157:H7 serotype. Except during outbreaks, STEC-HUS is less frequent in adults. The main route of transmission is the consumption of undercooked ground beef or unpasteurized dairy products, or household contacts with STEC diarrhea. Mortality is 1 to 2%. Half of patients require dialysis at the acute phase, the majority will recover normal renal function but approximately 30% will suffer renal sequelae. The risk of sequelae is important if the duration of anuria has been more than 5 days. Treatment of STEC-HUS is mostly supportive. The efficacy of plasma exchanges is not demonstrated and that of eculizumab, a complement blocker, especially in case of central nervous system or cardiac involvement, uncertain. Prevention of STEC-HUS relies on simple methods, often unknown of parents of young children, with the French general population being scarcely informed. However, the surveillance of STEC-infections/HUS by the Institut de veille sanitaire and the Reference Center for E. coli infections allows the early detection of outbreaks and their source of contamination. This prevents the emergence of new cases by withdrawing the suspected food from the market and diffusing the information to the population (return of suspected food).


Ultrastructural cytochemical identification of the siderophilic enterocyte.
Specific iron-binding sites in the gut were visualized by the sequential incubation of glutaraldehyde-fixed specimens in iron nitrilotriacetate (FeNTA) and acid ferro-cyanide (AF). In rat duodenum, jejunum, and ileum, approximately half of the enterocytes from the crypt to the distal villus contained FeNTA-AF-reactive material. The staining intensity of individual enterocytes appeared to decrease progressively in more distal locations in the gut. Maximal FeNTA-AF staining was observed in cells in the upper half of the villus, and was localized primarily in microvilli, apical cytoplasm, and lateral membranes. In duodenal crypt cells, stain deposits were present primarily in the microvilli. FeNTA-AF stained sites in the cytoplasmic and microvillus matrix were approximately 100-fold greater in number than were sites of intrinsic iron stained with AF alone. FeNTA-AF and AF staining in human duodenal enterocytes was similar to that observed in rat duodena, demonstrating the applicability of this methodology to human samples. In rat duodena, the distribution of AF staining alone in specimens taken 10 min after the in vivo intraduodenal administration of FeCl2 was similar to that of FeNTA-AF staining in tissue from fasted animals not given iron. The distribution and frequency of iron-binding sites stainable with the FeNTA-AF method which occur in a subpopulation of enterocytes can be correlated closely with physiologic, histologic, and ultrastructural parameters of inorganic iron absorption previously reported.


Terbinafine and risperidone drug interaction contributing to clinical changes in a forensic psychiatric patient.
Risperidone is a second generation "atypical" antipsychotic that exhibits its clinical effects through a combined effort of risperidone and its active metabolite, 9-hydroxyrisperidone (9-OHR), otherwise known as paliperidone. Risperidone is hepatically metabolized by the cytochrome P450 2D6 (CYP2D6) enzyme into 9-OHR. Significant interference with the metabolism of risperidone may lead to clinical consequences for patients via alterations in the ratio of the parent compound and active metabolite. This patient case reports 1 example of how a drug interaction could contribute to delayed response to a medication increase after psychiatric decompensation. A forensic psychiatric patient was transitioned from oral risperidone to risperidone microspheres long-acting injectable and had worsening of symptoms, necessitating an increased dose of the injection. This increase in symptoms may have been prolonged by addition of a CYP2D6 inhibitor, terbinafine. The changes in clinical symptoms correlate with medication concentrations that were drawn before terbinafine was started, during terbinafine therapy, and after terbinafine was discontinued.


Appraisal of phytochemical and in vitro biological attributes of an unexplored folklore: Rhus Punjabensis Stewart.
The role of plants for discovery of therapeutic potential accentuates the need to know their biological attributes. The present study aims to comprehend the biological attributes of Rhus punjabensis, an unexplored traditional medicinal plant. Leaf and stem extracts of R. punjabensis prepared in 11 different organic solvents are evaluated for multimode antioxidant potential, total phenolic and flavonoid contents were determined through colorimetric assays, HPLC-DAD analysis was carried out for quantification of various polyphenols in extracts. Brine shrimp lethality, SRB and MTT assays were used to elucidate plant's cytotoxic and antileishmanial potentials. Disc diffusion assay was used to elucidate the protein kinase inhibitory, antibacterial and antifungal spectrum. Ethanol + ethyl acetate yielded maximum extract recovery from leaf (6.11 ± 1.09% w/w), total phenolic content (80.5 ± 2.18 μg GAE/mg extract) and reducing power potential (165.4 ± 2.29 μg AAE/mg extract). Maximum flavonoid content (30.50 ± 1.11 μg QE/mg extract) and highest DPPH based free radical scavenging activity (IC50 11.4 ± 2.07) was exhibited by the methanol + chloroform leaf extract. The methanol extract showed maximum total antioxidant capacity (74.5 ± 2.25 μg AAE/mg DW), protein kinase inhibitory (12.5 ± 1.10 bald phenotype at 100 μg/disc) and antifungal (MIC = 25 μg/disc against Aspergillus flavus) potential. Reverse phase HPLC-DAD based quantification reveals presence of gallic acid, apigenin, rutin and catechin in various extracts. Brine shrimp lethality assay demonstrated most extracts as highly cytotoxic (LC50 < 50 μg/mL) whereas chloroform extract of leaf demonstrated maximuminhibition against human leukemia cell line (IC50 7.80 ± 0.01 μg/mL). A significant activity against leishmanial promastigotes was demonstrated by n-hexane leaf extract (IC50 = 15.78 ± 0.15 μg/mL). A better antibacterial activity,by the extracts, against Gram positive strains as compared to Gram negative was observed. Results recommend multiple-solvent system as a critical factor to sumptuous the biological prospective of R. punjabensis and propose it to be a useful natural hub for the discovery of novel antioxidant, anticancer, antileishmanial and antimicrobial agents.


Sequential combination of pyrazofurin and 5-azacytidine in patients with acute myelocytic leukemia and carcinoma.
The combination of pyrazofurin (PF) and 5-azacytidine (5-aza-CR) was evaluated in 12 patients with neoplastic diseases who had failed conventional therapies. They included 6 patients with acute myelocytic leukemia (AML) and 6 with various carcinomas. PF was given by i.v. bolus at doses ranging from 25 to 200 mg/m2 followed by 5-aza-CR given by continuous 24-hour infusion at doses ranging from 30 to 120 mg/m2/24 h during 40-ic diseases who had failed conventional therapies. They included 6 patients with acute myelocytic leukemia (AML) and 6 with various carcinomas. PF was given by i.v. bolus at doses ranging from 25 to 200 mg/m2 followed by 5-aza-CR given by continuous 24-hour infusion at doses ranging from 30 to 120 mg/m2/24 h during 40-ic diseases who had failed conventional therapies. They included 6 patients with acute myelocytic leukemia (AML) and 6 with various carcinomas. PF was given by i.v. bolus at doses ranging from 25 to 200 mg/m2 followed by 5-aza-CR given by continuous 24-hour infusion at doses ranging from 30 to 120 mg/m2/24 h during 40--120 h. Dose-limiting toxicity was mucocutaneous, which appeared in 11/17 courses. Skin rash was similar to that produced by PF alone, but was present after much lower doses of PF when followed by 5-aza-CR. Moderate and reversible thrombocytopenia and leukopenia occurred in 3/6 patients with carcinoma. No objective response was seen in patients with carcinoma, and no marrow remission occurred in patients with AML. 24-Hour urinary excretion of orotidine and oroticacid were measured during 11 courses in 8 patients, and were not much different than those obtained previously with PF alone. The occurrence of mucocutaneous toxicity precluded the use of higher doses of PF and 5-aza-CR, which might have been therapeutically more active.


Structure and reaction mechanism of L-arginine:glycine amidinotransferase.
L-Arginine:glycine amidinotransferase (AT) catalyzes the committed step in creatine biosynthesis by formation of guanidinoacetic acid, the direct precursor of creatine. The X-ray structure of the human enzyme shows a novel fold with fivefold pseudosymmetry of beta beta alphabeta-modules. These modules enclose the active site compartment of the basket-like structure. The active site of AT lies at the bottom of a very narrow channel and contains a catalytic triad with the residues Cys-His-Asp. The transamidination reaction follows a ping-pong mechanism and is accompanied by large conformational changes. During catalysis the amidino group is covalently attached to the active site cysteine to give an amidino-cysteine intermediate.


Fresh water fishes as indicators of Kaveri River pollution.
The survey of fish fauna in Kaveri River at polluted and unpolluted sites revealed a direct effect on the distribution of fishes in that 14 species were observed in unpolluted site and only 6 species in polluted site. Further, the haemotological parameters like RBC, WBC and haemoglobin content increased in fishes collected from polluted site whereas the organic constituents of muscle decreased in the above fishes when compared to the fishes of unpolluted site. The reason for the above changes is discussed.


Revisiting the launching of the Kennedy Institute: re-visioning the origins of bioethics.
Twenty-five years ago, on October 1, 1971, at a press conference held at Georgetown University, the Joseph and Rose Kennedy Institute for the Study of Human Reproduction and Bioethics, later called the Kennedy Institute of Ethics, was offically inaugurated. To revisit that event -- and the Institute's five founding collaborators who spoke at it -- provides an opportunity to re-vision some of the most significant intellectual, moral, cultural, and political factors that shaped both this Institute and the then-nascent field of bioethics.


Three-Dimensional Polydopamine Functionalized Coiled Microfibrous Scaffolds Enhance Human Mesenchymal Stem Cells Colonization and Mild Myofibroblastic Differentiation.
Electrospinning has been widely applied for tissue engineering due to its versatility of fabricating extracellular matrix (ECM) mimicking fibrillar scaffolds. Yet there are still challenges such as that these two-dimensional (2D) tightly packed, hydrophobic fibers often hinder cell infiltration and cell-scaffold integration. In this study, polycaprolactone (PCL) was electrospun into a grounded coagulation bath collector, resulting in 3D coiled microfibers with in situ surface functionalization with hydrophilic, catecholic polydopamine (pDA). The 3D scaffolds showed biocompatibility and were well-integrated with human bone marrow derived human mesenchymal stem cells (hMSCs), with significantly higher cell penetration depth compared to that of the 2D PCL microfibers from traditional electrospinning. Further differentiation of human mesenchymal stem cells (hMSCs) into fibroblast phenotype in vitro indicates that, compared to the stiff, tightly packed, 2D scaffolds which aggravated myofibroblasts related activities, such as upregulated gene and protein expression of α-smooth muscle actin (α-SMA), 3D scaffolds induced milder myofibroblastic differentiation. The flexible 3D fibers further allowed contraction with the well-integrated, mechanically active myofibroblasts, monitored under live-cell imaging, whereas the stiff 2D scaffolds restricted that.


Pattern formation on silicon by laser-initiated liquid-assisted colloidal lithography.
We report sub-diffraction limited patterning of Si substrate surfaces by laser-initiated liquid-assisted colloidal lithography. The technique involves exposing a two-dimensional lattice of transparent colloidal particles spin coated on the substrate of interest (here Si) immersed in a liquid (e.g. methanol, acetone, carbon tetrachloride, toluene) to a single picosecond pulse of ultraviolet laser radiation. Surface patterns formed using colloidal particles with different radii in the range 195 nm ≤ R ≤ 1.5 μm and liquids with differing indices of refraction (n(liquid)) are demonstrated, the detailed topographies of which are sensitively dependent upon whether the index of refraction of the colloidal particle (n(colloid)) is greater or smaller than n liquid (i.e. upon whether the incident light converges or diverges upon interaction with the particle). The spatial intensity modulation formed by diffraction of the single laser pulse by the colloidal particles is imprinted into the Si substrate.


Muscle Properties, Gross Motor Performance, and Quality of Life in Children With Sickle Cell Disease.
To explore muscle properties, gross motor performance, and quality of life (QoL) in children with sickle cell disease (SCD) compared with controls and to assess relationships among these outcomes. A cross-sectional study of 24 children assessed muscle properties including: knee extension strength by dynamometry; vastus lateralis (VL) and rectus femoris (RF) muscle thickness by ultrasonography; and VL and RF neuromuscular activation (rate of muscle activation [RoA]) by electromyography (EMG). Gross motor performance and QoL were assessed by standardized tests and questionnaires. Children with SCD had impaired knee extension strength, VL EMG RoA, gross motor performance, and QoL compared with children without SCD. Relationships among muscle properties, gross motor performance, and QoL were identified. These findings indicate that comprehensive muscle properties, gross motor performance, and QoL assessments should be considered to support and develop individualized physical therapy plans for children with SCD.


Development of CTL memory despite arrested clonal expansion.
Activation of a cytotoxic T lymphocyte (CTL) response in an antigen-exposed lymph node involves a great diversity of encounters between naive CTL and APC that differ in both duration and quality. This broad spectrum of priming events instigates a complex blend of CTL developmental pathways. Using an experimental system that allows tight control over CTL priming, we have singled out defined priming events and analyzed the impact of the resulting instructional program on the effector and memory phases of the CTL response. As expected, prolonged antigenic stimulation induces potent CTL expansion, effector function and CTL memory. In contrast, CTL that have received suboptimal stimulation fail to undergo extensive expansion. Nevertheless these arrested CTL persist long term and acquire memory function. Thus, our data demonstrate that CTL memory can develop as a result of a suboptimal stimulation that causes arrested clonal expansion.


Molecular adsorption on graphene.
Current studies addressing the engineering of charge carrier concentration and the electronic band gap in epitaxial graphene using molecular adsorbates are reviewed. The focus here is on interactions between the graphene surface and the adsorbed molecules, including small gas molecules (H(2)O, H(2), O(2), CO, NO(2), NO, and NH(3)), aromatic, and non-aromatic molecules (F4-TCNQ, PTCDA, TPA, Na-NH(2), An-CH(3), An-Br, Poly (ethylene imine) (PEI), and diazonium salts), and various biomolecules such as peptides, DNA fragments, and other derivatives. This is followed by a discussion on graphene-based gas sensor concepts. In reviewing the studies of the effects of molecular adsorption on graphene, it is evident that the strong manipulation of graphene's electronic structure, including p- and n-doping, is not only possible with molecular adsorbates, but that this approach appears to be superior compared to these exploiting edge effects, local defects, or strain. However, graphene-based gas sensors, albeit feasible because huge adsorbate-induced variations in the relative conductivity are possible, generally suffer from the lack of chemical selectivity.


From pixels to picograms: a beginners' guide to genome quantification by Feulgen image analysis densitometry.
The study of genome size variation is important from a number of practical and theoretical perspectives. For example, the long-standing "C-value enigma" relating to the more than 200,000-fold range in eukaryotic genome sizes is best studied from a broad comparative standpoint. Genome size data are also required in detailed analyses of genome structure and evolution. The choice of future genome sequencing projects will be dependent on knowledge regarding the sizes of genomes to be sequenced, and so on. To date, genome size data have been acquired primarily by Feulgen microdensitometry or flow cytometry. Each has several advantages but also important limitations. In this review, we provide a practical guide to the new technique of Feulgen image analysis densitometry. The review is designed for those interested in genome size measurements but not extensively experienced in histochemistry, densitometry, or microscopy. Therefore, relevant historical and technical background information is included. For easy reference, we provide recipes for required reagents, guidelines for cell staining, and a checklist of steps for successful image analysis. We hope that the accuracy, rapidity, and cost-effectiveness of Feulgen image analysis demonstrated here will stimulate further surveys of genome sizes in a variety of taxa.


Effects of trivalent chromium on hepatic CYP-linked monooxygenases in laying hens.
Chromium is an essential nutrient required for the metabolism of carbohydrates and lipids in humans and many animal species. We evaluated whether feeding laying hens with high levels of different chemical forms of trivalent chromium may affect hepatic metabolizing cytochrome P-450 (CYP)-linked enzymes. Modulation of CYP-dependent monooxygenases (which play a pivotal role in the endogenous metabolism) by Cr(III) was tested using either specific substrates as probes of different CYPs or testosterone as a multi-bioprobe. The CYP-supported oxidases were studied in liver microsomes from laying hens fed with diet supplemented with either 25 or 50 ppm chromium chloride as a yeast or as aminoniacinate. Although at 25 ppm no appreciable effects were observed, at 50 ppm a general inactivation of the recorded monooxygenases (ranging from 34% loss for ethoxycoumarin O-deethylase with chromium chloride to 85% loss for O-deethylation of ethoxyresorufin with either chromium yeast or aminoniacinate) were achieved in the supplemented groups vs controls. The only exception was the O-dealkylation of pentoxyresorufin, which was significantly boosted by both chromium yeast (up to 65% increase) and chromium aminoniacinate (up to 141%). Measurements of the regio- and stereoselective hydroxylation of testosterone used as a multi-bioprobe corroborated the inactivating properties of Cr(III) at the higher dose. Taken as a whole, these findings seem to indicate that high levels of Cr(III) supplementation can substantially impair CYP-catalysed drug metabolism in laying hens.


[Use of Bronchial Blockers for Lung Isolation].
Traditionally the double-lumen-tube (DLT) is considered the gold standard for lung separation. Despite being equally feasible for standard situations, there are special populations and circumstances requiring the use of a bronchial blocker (BB) to establish one-lung ventilation. Children under 8 years of age and patients without a patent orotracheal airway necessitate the use of a bronchial blocker in most cases, as well as those requiring selective lobar blockade or a rapid sequence induction. Surgery with predicted postoperative mechanical ventilation or in tracheotomized patients at least favors their use by avoiding the complications of a tube exchange. Bronchial blocker models currently in clinical use include the wire-guided Arndt-Blocker, the Flexitip Cohen-Blocker, the Fuji Uniblocker, the Y-shaped EZ-Blocker and the tracheoscopy-guided VivaSight-EB. Their common concept is the occlusion of the operative lung by the inflation of their distal balloon, with the deflation of that lung occurring through their inner lumen. They mainly differ in their mode of placement. Bronchial blockers offer a clinical performance comparable to the DLT. Placement times for lung isolation devices and surgical exposure may depend more on the experience of the anaesthetist than the device itself. Bronchial blockers won't replace the DLT as gold standard at least due to their cost of acquisition, but provided adequate training outside of the emergency situation, their utilisation offers equal operative conditions at comparable placement times, dislocation rates and ease of use. A modern bronchial blocker should be available in institutions managing complex thoracic cases.


Characterization of Bioactive Compounds, Mineral Content, and Antioxidant Activity in Bean Varieties Grown with Traditional Methods in Oaxaca, Mexico.
The aim of the current study is to characterize the bean varieties produced in the State of Oaxaca (Mexico) with the purpose of selecting varieties with the potential of being biofortified with micronutrients. Eleven bean varieties representative of the State of Oaxaca (Mexico) were harvested, the color was characterized and the physicochemical analysis, mineral content, antioxidant capacity, reducing power, and bioactive compounds were determined. Data obtained were subjected to a variance analysis for the difference between the means of the bean varieties studied through the 95% Tukey test. The results obtained show the significant difference was found among the 11 bean varieties harvested in Oaxaca (México). The analysis found five outstanding varieties with a larger quantity of favorable characteristics on the iron, zinc, protein content, antioxidant capacity and reducing power. The outstanding varieties relating Fe and Zn content were Michigan for Fe 67.4 ppm, Sangre de Toro 62.4 ppm, which showed the larger content of antioxidant capacity (82.12%) scavenging activity and Biche for Zn 34.7 ppm. The variety with a larger quantity of protein (26.66%) was Biche bean, followed by the Peruano bean with 24.91% of protein. The variety with larger content of reducing power 0.16% was Blanco Michigan bean. Lastly, it is also remarkable that such outstanding bean varieties are important to include in a biofortification program with micro-nutrients to improve the food safety and the nutrition in vulnerable communities of the urban and rural sector of Oaxaca (Mexico).


Understanding water conservation vs. profligation traits in vegetable legumes through a physio-transcriptomic-functional approach.
Vegetable soybean and cowpea are related warm-season legumes showing contrasting leaf water use behaviors under similar root drought stresses, whose mechanisms are not well understood. Here we conducted an integrative phenomic-transcriptomic study on the two crops grown in a feedback irrigation system that enabled precise control of soil water contents. Continuous transpiration rate monitoring demonstrated that cowpea used water more conservatively under earlier soil drought stages, but tended to maintain higher transpiration under prolonged drought. Interestingly, we observed a soybean-specific transpiration rate increase accompanied by phase shift under moderate soil drought. Time-series transcriptomic analysis suggested a dehydration avoidance mechanism of cowpea at early soil drought stage, in which the VuHAI3 and VuTIP2;3 genes were suggested to be involved. Multifactorial gene clustering analysis revealed different responsiveness of genes to drought, time of day and their interactions between the two crops, which involved species-dependent regulation of the circadian clock genes. Gene network analysis identified two co-expression modules each associated with transpiration rate in cowpea and soybean, including a pair of negatively correlated modules between species. Module hub genes, including the ABA-degrading gene GmCYP707A4 and the trehalose-phosphatase/synthase gene VuTPS9 were identified. Inter-modular network analysis revealed putative co-players of the hub genes. Transgenic analyses verified the role of VuTPS9 in regulating transpiration rate under osmotic stresses. These findings propose that species-specific transcriptomic reprograming in leaves of the two crops suffering similar soil drought was not only a result of the different drought resistance level, but a cause of it.


NADPH Oxidases, Angiogenesis, and Peripheral Artery Disease.
Peripheral artery disease (PAD) is caused by narrowing of arteries in the limbs, normally occurring in the lower extremities, with severe cases resulting in amputation of the foot or leg. A potential approach for treatment is to stimulate the formation of new blood vessels to restore blood flow to limb tissues. This is a process called angiogenesis and involves the proliferation, migration, and differentiation of endothelial cells. Angiogenesis can be stimulated by reactive oxygen species (ROS), with NADPH oxidases (NOX) being a major source of ROS in endothelial cells. This review summarizes the recent evidence implicating NOX isoforms in their ability to regulate angiogenesis in vascular endothelial cells in vitro, and in PAD in vivo. Increasing our understanding of the involvement of the NOX isoforms in promoting therapeutic angiogenesis may lead to new treatment options to slow or reverse PAD.


Health-related quality of life of children with newly diagnosed specific learning disability.
The objective of this study was to measure health-related quality of life (HRQL) of children with newly diagnosed specific learning disability (SpLD) using the Child Health Questionnaire-Parent Form 50. We detected clinically significant deficits (effect size > or = -0.5) in 9 out of 12 domains: limitations in family activities, emotional impact on parents, social limitations as a result of emotional-behavioral problems, time impact on parents, general behavior, physical functioning, social limitations as a result of physical health, general health perceptions and mental health; and in both summary scores (psychosocial > physical). Multivariate analysis revealed having > or = 1 non-academic problem(s) (p < 0.0001), attention-deficit hyperactivity disorder (p = 0.005) or first-born status (p = 0.009) predicted a poor psychosocial summary score; and having > or =1 non-academic problem(s) (p = 0.006) or first-born status (p = 0.035) predicted a poor physical summary score. HRQL is significantly compromised in children having newly diagnosed SpLD.


Never say never: Identification of acute pulmonary embolism on non-contrast computed tomography imaging.
Acute undifferentiated illness remains a critical challenge for the emergency physician. The diagnostic evaluation and treatment decisions on such severely ill patients often needs to be made in an expedited fashion. Situations occur wherein the ideal or recommended workup is not always feasible due to time or patient specific factors. We present two cases of patients with undifferentiated acute illness who had undergone non-contrast CT (computed tomography) scanning and subsequently had central pulmonary embolism identified upon careful review of their CT studies.


Association of migraine with asthma risk: A retrospective population-based cohort study.
Both migraine and asthma are common health problems in the general population. However, the association between these two disorders is yet to be fully explored. We examined whether adult patients with migraine are at a higher risk of asthma development. We used data retrieved from the National Health Insurance Research Database in Taiwan to conduct this nationwide population-based cohort study. We identified 6647 patients aged 20-60 years who were newly diagnosed with migraine between 2000 and 2005 for the migraine group and identified 26 588 patients without migraine for the nonmigraine group. Both groups were followed up until the end of 2011 to examine the incidence of asthma. Cox proportional hazards regression analysis was used to measure the hazard ratio (HR) of asthma in the migraine group compared with the nonmigraine group. The HR of asthma development was 1.37 (95% confidence interval = 1.21-1.56) for the migraine group compared with the nonmigraine group after adjustment for age, sex, occupational status, insurance premium, urbanization, comorbidities, and annual outpatient department visits. Further stratified analysis revealed that this risk was also significantly higher for both sexes and in the 40- to 60-year age group. The main limitation of this study was that some relevant data were unavailable, such as pain medication prescriptions and family history of migraine and asthma. Adult patients with migraine are at a higher future risk of asthma development.


Relative deprivation in black and white youth: an empirical investigation.
A model of relative deprivation is proposed drawing on the writings of Gurr (1970) and Runciman (1966) and is discussed in relation to existing studies. Those aspects of the model concerning the intensity of affective reaction to relative deprivation are subjected to empirical test using samples of employed and unemployed black and white youth. The prediction that the degree of relative deprivation is negatively associated with attitudes to the perceived cause of deprivation receives only limited support. Various indices of relative deprivation are compared and it is concluded that present relative deprivation is the most appropriate operational measure. It is concluded that in understanding the attitudes of black and white youth to societal institutions other social characteristics are more important then relative deprivation.


Mixed squamous cell and glandular papilloma of the lung: A case report of a novel mutation in the BRAF gene and coexistent HPV infection, possible relationship to ciliated muconodular papillary tumor.
Mixed squamous cell and glandular papilloma (mixed papilloma) is a very rare tumor, with fewer than 25 cases having been reported in the literature. Although a scattering of cases of p16Ink4a overexpression have been described to date, no human papillomavirus (HPV) DNA has been detected in these tumors, either by in situ hybridization (ISH) or polymerase chain reaction (PCR). This is the first case of mixed papilloma with PCR-confirmed HPV genotype 16, 35, 51 infections in an 18-year-old non-smoking male, coexisting with multiple atypical adenomatous hyperplasias (AAHs). Histologically, this tumor shows a predominant papillary architecture, covered by a mixture of stratified squamous cells, ciliated or non-ciliated cuboidal to columnar cells, mucous cells, and scattered goblet cells. Immunohistochemically, the squamous component was positive for p40, and the glandular cells were focally positive for TTF-1. Both components were diffusely immunoreactive to CK7. In addition, BRAF V600E mutation was also first demonstrated in mixed papilloma, but not in the AAHs. These findings suggest that HPV infection and the BRAF mutation may be important in the pathogenetic role in young non-smoking patients.


[T-cell lymphoma associated with sprue].
A 47-year-old woman, known to have coeliac disease, developed bouts of fever, up to 39 degrees C, with loss of weight and treatment-resistant diarrhoea, as well as swelling of the submandibular, axillary and inguinal lymph nodes. Tests revealed a pancytopenia (haemoglobin 8.8 g/dl, leucocytes 500/microliter, platelets 19,000/microliter), and a reduction of the Quick value to 39%. Computer tomography demonstrated extensive abdominal lymphomas. The patient's general condition quickly deteriorated, hypoproteinaemia developed (total protein 4.6 g/dl) with peripheral oedema, ascites and pleural effusion. She died before the suspected diagnosis of coeliac disease-associated malignant lymphoma could be confirmed. Autopsy demonstrated a highly malignant, pleomorphic, primary abdominal non-Hodgkin lymphoma, immunohistologically a T-cell lymphoma.


Effects of gaze and speech rate on receivers' evaluations of persuasive speech.
This study examined how gaze and speech rate affect perceptions of a speaker. Participants viewed a video recording of one of four persuasive messages delivered by a female speaker. Analysis of speech rate, gaze, and listener's sex revealed that when combined with a small amount of gaze, slow speech rate decreased trustworthiness as compared to a fast speech rate. For women, slow speech rate was thought to be indicative of less expertise as compared to a fast speech rate, again when combined with low gaze. There were no significant interactions, but there were main effects of gaze and speech rate on persuasiveness. High levels of gaze and slow speech rate each enhanced perceptions of the speaker's persuasiveness.


Two independent effects of cortisol on chicken liver.
Activities of two key enzymes of glycogen metabolism have been measured after an acute administration of cortisol to 3d-old chickens. Glycogen synthase activity is enhanced 2-3 hours after a cortisol injection, and this activation is blocked by use of protein synthesis inhibitors. Glycogen phosphorylase activity is enhanced at an early stage, and this effect is not suppressed by protein synthesis inhibitors. Liver cAMP levels are not increased concomitantly with this early activation of glycogen phosphorylase; indeed they are depleted. These results point to the existence of an effect of cortisol previous to and independent of its nuclear interaction, and not mediated by an activation of the membrane adenylate cyclase.


Practical considerations regarding the use of total nutrient admixtures.
The biological concerns, proper storage and administration, and advantages of using total nutrient admixtures (TNAs) for nutritional support are reviewed. In 1983, FDA approved lipid emulsions for administration with dextrose and selected crystalline amino acid preparations (known as three-in-one or total nutrient admixtures). The stability of TNAs is affected by pH, order of mixing, and temperature. Conflicting results have been reported on the issue of microbial growth potential in TNAs. At room temperature, the delivery of the TNA infusate should not exceed 24 hours. Plastic containers that do not contain diethylhexyl phthalate, in sizes up to 3 L, are practical and safe for administration of TNAs. The efficiency of an institution's volumetric pumps should be evaluated before converting to a TNA system because the low final concentrations of lipid emulsion present in the admixtures may render certain pumps inoperable. The practical, nutritional, and potential economic benefits of a TNA delivery system support its use. Further research is needed to determine microbial growth potential, electrolyte and drug compatibilities, and stability under prolonged storage of these admixtures.


Tobacco use and oral hygiene as risk indicators for periodontitis.
To detect the periodontal status of male smokers and betel chewers in a rural community in Sri Lanka and compare it with that of male non-tobacco users of the same community. A cross-sectional community based study was carried out in a sample of 2277 rural adult males aged 20-60 years, adopting multistage cluster sampling technique. The present analysis was confined to 2178 subjects who were mutually exclusive smokers, betel chewers or non-tobacco users. The periodontal status was assessed by clinical measurement of levels of bacterial plaque (PLI), gingival inflammation (GI) and loss of epithelial attachment (LA). All measurements were carried out on four sites of all teeth present except third molars and the mean values for periodontal parameters were calculated. Bivariate analysis revealed that the overall periodontitis levels were significantly higher in betel chewers and smokers than in non-tobacco users. Multiple linear regression analysis showed that there were no significant effects of smoking and betel chewing per se on LA, independent of age, socioeconomic status (SES) and whether or not controlled for PLI. The effect of the quantified tobacco use on LA was statistically significant regardless of age, PLI or SES. However, the effect of the quantified tobacco use was considered limited when compared to that of oral hygiene. The findings highlighted the importance of oral hygiene in the aetiology of periodontitis while confirming the statistical significance of the quantified tobacco use on LA. Oral hygiene and the quantified tobacco use may be considered as risk indicators for periodontitis.


A cohort study of initial self-harm events: method-specific case fatality of index events, predictors of fatal and nonfatal repetition, and frequency of method-switching.
Most studies evaluating self-harm repetition risk factors are from Asia and Europe, use cohorts of people who self-injure without differentiating incident and prevalent self-harm episodes, and do not stratify by suicide method. The current study uses an incident user design to (a) examine case fatality at index self-harm events and at each repeat event, by method, (b) describe method-switching, and (c) identify factors associated with repetition of self-harm among those who survive their index hospitalization. Specifically, this study reports psychiatric history and method-specific case fatality for the initial self-harm event among Utah residents with an index event in 2014 or 2015 and who have no history of prior self-harm in hospital records. For survivors of the index self-harm episode, we use Accelerated Failure Time models to identify risk factors for nonfatal repetition and separately for suicide. Key findings: 10,521 Utah residents with no 3-year self-harm hospital history experienced a 2014 or 2015 index event. Of the 9.5% with index deaths, 53.6% used firearms. Of the 90.5% who survived, 63.1% used drugs. Among the index nonfatal cases, over an average 1-year follow-up, 11.7% experienced a nonfatal repetition and 0.8% died by suicide. Most subsequent nonfatal repetitions (59.7%) and suicides (56.8%) had presented with an index drug poisoning; over half (56.8%) of those who died switched methods. For those who subsequently fatally self-harmed, most used poisoning by drugs (33.8%), hanging/strangulation (28.4%), or firearms (24.3%) in the terminal episode. Nonfatal repetition was associated with younger age, index cutting/piercing instruments, and past-year psychiatric and drug abuse diagnoses. Subsequent suicide was associated with male gender, older age, and index gas poisoning and hanging/suffocation. Of the 56 people who survived an index firearm event, none subsequently died by suicide during the study period.


The operation of a ward-based radiology consultation service.
A radiology consultation service, consisting of an attending radiologist and a senior radiology resident, functioned for ten months on an acute care medical ward in a teaching hospital. The consultants conducted daily conferences during which they discussed, approved, and scheduled all imaging tests. During the study interval, there were significantly fewer procedures performed on patients in the consultation ward than were performed on patients in three other medical wards of the hospital. The service was well accepted by the medical staff. Early and sustained participation by a radiologist who functions as an advisor during diagnostic evaluations can help limit inappropriate or redundant imaging examinations.


Medical laboratory accreditation: a Hong Kong perspective.
This is an account of the accreditation of the Surgical Pathology, Cytopathology, Autopsy Service, Haematology, Blood Bank, Bone Marrow Transplant and Electronmicroscopy Laboratories of the Department of Anatomical and Cellular Pathology, the Prince of Wales Hospital, Shatin, New Territories, Hong Kong, SAR, China, the first of their category to be accredited in the Special Administrative Region. The Australian-based National Association of Testing Authorities (NATA) used standards formulated by the National Pathology Accreditation Advisory Council (NPAAC) to measure the performance of the laboratory sections and to determine whether the laboratory service was of a sufficient standard to be granted accreditation. Some practices dating back to the colonial period required attention, while eliciting the support of staff at all levels was essential for achieving accreditation. Some cultural factors had to be taken into account when implementing changes. Finally, successful accreditation has provided the impetus for other Hong Kong laboratories to become accredited and this will have a beneficial flow-on effect for the entire region.


Assessment of the Safety and Effectiveness of Colorectal Robotic-Assisted Surgery: The First 50 Consecutive Cases at a Single Centre.
Colorectal robotic-assisted-surgery (RAS) is a novel technology with scarce real-world evidence. The aim of this retrospective review was to ascertain the safety and effectiveness of colorectal RAS. The da Vinci® Xi™ robot system (Intuitive Surgical, Inc., Sunnyvale, CA, USA) was used to perform the first 50 colorectal resections in our centre. Outcomes regarding safety and efficacy were analysed and learning curves (LC) were plotted using RStudio. The median patient age and BMI were 65 years (IQR, 50.25-76.5) and 28.3kg/m2 (IQR, 25.2-30.7), respectively, and 27 patients were female. Malignancy (66%) followed by rectal prolapse (18%) was the most frequent diagnosis, and all malignant tumours were completely resected. High anterior resection was the most frequently performed operation (36%). The median operative time was 256.5 minutes (IQR, 202.2-332.8). Twenty-seven patients had anastomosis (54%), a stoma was formed in 7 (14%) and 7 anastomoses required defunctioning loop ileostomy (14%). Two unexpected intra-operative events occurred, and neither required conversion to an open procedure. Thirty-eight complications occurred in 21 patients, and most were minor by the Clavien-Dindo classification: CD 1 (17, 44.7%) or 2 (11, 28.9%). Moreover, 5 patients developed an anastomotic leak (14.7%), 5 developed infections (10%), 2 required transfusions (4%) and 3 needed re-operation (6%). There was no 30-day mortality and the readmission rate was 8%. The median length of stay in hospital was 6 days (IQR,4-8). All resections, except for low anterior resections, resulted in a significantly longer stay compared to rectopexies. Finally, projections from LCs indicated that outcome optimization can be achieved after experience with 33-39 cases. Colorectal RAS in our centre was both safe and effective. In the initial 50 cases, there was no 30-day mortality and no need for conversion to an open surgery. The readmission and complication (>CD 2) rates were 8% and 20%, respectively.


Blood pressure in children with obstructive sleep apnea.
Hypertension is a common complication of obstructive sleep apnea in adults. However, hypertension has not been studied systematically in children with the obstructive sleep apnea syndrome (OSAS). We therefore measured blood pressure (BP) during polysomnography in 41 children with OSAS, compared to 26 children with primary snoring (PS). Systolic and diastolic BP were measured every 15 min via an appropriately sized arm cuff, using an automated system. This was tolerated by the children without inducing arousals from sleep. Children with OSAS had a significantly higher diastolic BP than those with PS (p < 0.001 for sleep and p < 0.005 for wakefulness). There was no significant difference in systolic BP between the two groups. Multiple linear regression showed that blood pressure could be predicted by apnea index, body mass index, and age. Blood pressure during sleep was lower than during wakefulness (p < 0.001 for diastole and p < 0.01 for systole), but did not differ significantly between rapid eye movement (REM) and non-REM sleep. We conclude that childhood OSAS is associated with systemic diastolic hypertension.


Human serine racemase structure/activity relationship studies provide mechanistic insight and point to position 84 as a hot spot for β-elimination function.
There is currently great interest in human serine racemase, the enzyme responsible for producing the NMDA co-agonist d-serine. Reported correlation of d-serine levels with disorders including Alzheimer's disease, ALS, and ischemic brain damage (elevated d-serine) and schizophrenia (reduced d-serine) has further piqued this interest. Reported here is a structure/activity relationship study of position Ser84, the putative re-face base. In the most extreme case of functional reprogramming, the S84D mutant displays a dramatic reversal of β-elimination substrate specificity in favor of l-serine over the normally preferred l-serine-O-sulfate (∼1200-fold change in kcat/Km ratios) and l (l-THA; ∼5000-fold change in kcat/Km ratios) alternative substrates. On the other hand, the S84T (which performs l-Ser racemization activity), S84A (good kcat but high Km for l-THA elimination), and S84N mutants (nearly WT efficiency for l-Ser elimination) displayed intermediate activity, all showing a preference for the anionic substrates, but generally attenuated compared with the native enzyme. Inhibition studies with l-erythro-β-hydroxyaspartate follow this trend, with both WT serine racemase and the S84N mutant being competitively inhibited, with Ki = 31 ± 1.5 μm and 1.5 ± 0.1 mm, respectively, and the S84D being inert to inhibition. Computational modeling pointed to a key role for residue Arg-135 in binding and properly positioning the l-THA and l-serine-O-sulfate substrates and the l-erythro-β-hydroxyaspartate inhibitor. Examination of available sequence data suggests that Arg-135 may have originated for l-THA-like β-elimination function in earlier evolutionary variants, and examination of available structural data suggests that a Ser84-H2O-Lys114 hydrogen-bonding network in human serine racemase lowers the pKa of the Ser84re-face base.


Atypical femoral fractures during prolonged use of bisphosphonates: short-term responses to strontium ranelate and teriparatide.
Atypical femoral fractures have rarely been reported in women taking bisphosphonates, but this is still a controversial issue. Data are derived mainly from observation studies because a post hoc analysis from a randomized clinical trial did not find any such association. The aim of this study was to report three cases of what are considered atypical femoral fractures and their responses to the use of strontium ranelate and teriparatide. We studied three postmenopausal women with a diagnosis of osteoporosis who suffered fractures of the subtrochanteric region and femoral diaphysis with no major trauma while on long-term use of bisphosphonates. All the major features of atypical femoral fractures highlighted in the Task Force Report of the American Society for Bone and Mineral Research were present in the three cases. They had had unconsolidated fractures for approximately 1 yr before being referred to our center. After 3 months on strontium ranelate 2 g/d, serum osteocalcin and serum β-carboxyterminal telopeptide had increased in case 1 by 125 and 100%, respectively, and in case 2 by 50 and 22%, respectively, with total closure of the fracture. In case 3, after 1 month on teriparatide 20 μg/d, a radiographic closure of the fracture was achieved, and 3 months later serum osteocalcin and serum β-carboxyterminal telopeptide had increased by 300 and 22%, respectively. Our finding showed that both teriparatide and strontium ranelate had a rapid bone anabolic effect on unhealed atypical fractures associated with chronic bisphosphonate use.


Subjective perception of sleep benefit in Parkinson's disease: Valid or irrelevant?
The phenomenon of sleep benefit (SB) in Parkinson's disease (PD), whereby waking motor function is improved despite no dopaminergic treatment overnight, is controversial. Previous studies suggested a significant discrepancy between subjective functional and objective motor improvement. The aim of this study was to determine how well subjective reporting of SB correlates with objective measures and if true motor improvement can be predicted by a standardized questionnaire. Ninety-two patients with PD participated. A structured questionnaire was developed to assess subjective SB. Quantitative motor assessment was performed using a validated smartphone application. Objective motor SB was considered to be present when the waking motor function was similar or superior to the daytime on-state. Twenty (22%) patients showed objective motor improvement on waking compared to end-of-dose. Most patients (77%) reported subjective SB without corresponding objective motor benefit. Our structured questionnaire could not predict Motor SB. The ability to delay morning medications and a perception of indifference or paradoxical worsening following the morning levodopa dose may suggest Motor SB. Most patients experience subjective SB with no measureable motor improvement. This perceived benefit could be related to non-motor improvement that is distinctly different to objective motor benefit.


Weighting climate model projections using observational constraints.
Projected climate change integrates the net response to multiple climate feedbacks. Whereas existing long-term climate change projections are typically based on unweighted individual climate model simulations, as observed climate change intensifies it is increasingly becoming possible to constrain the net response to feedbacks and hence projected warming directly from observed climate change. One approach scales simulated future warming based on a fit to observations over the historical period, but this approach is only accurate for near-term projections and for scenarios of continuously increasing radiative forcing. For this reason, the recent Fifth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC AR5) included such observationally constrained projections in its assessment of warming to 2035, but used raw model projections of longer term warming to 2100. Here a simple approach to weighting model projections based on an observational constraint is proposed which does not assume a linear relationship between past and future changes. This approach is used to weight model projections of warming in 2081-2100 relative to 1986-2005 under the Representative Concentration Pathway 4.5 forcing scenario, based on an observationally constrained estimate of the Transient Climate Response derived from a detection and attribution analysis. The resulting observationally constrained 5-95% warming range of 0.8-2.5 K is somewhat lower than the unweighted range of 1.1-2.6 K reported in the IPCC AR5.


Vasoactivity of adrenaline in regions covering the canine gastrointestinal tract.
Little is known about the action adrenaline has on vascular areas of functionally different parts of the stomach and intestine. Therefore the vasoactivity of adrenaline (1-1024 ng/kg i.v.) was studied by electromagnetic flow measurements in 8 vascular beds covering the gastrointestinal tract. Adrenaline induced 1) a vasodilation in the lesser curvature and antrum of the stomach; 2) a vasoconstriction in the greater curvature of the stomach; 3) a vasoconstriction followed by a vasodilation in the duodenum and jejunum; 4) a vasoconstriction in the ileum, caecum/colon and colon/rectum. Phenoxybenzamine (750 micrograms/kg i.v.) blocked systematically the vasoconstriction in the duodenum and jejunum but not in the ileum and colon. Vasodilation could be blocked by propranolol (100 micrograms/kg i.v.). It is concluded that 1) adrenaline-effects are mediated predominantly by beta-receptors in the antrum and lesser curvature of the stomach; predominantly by alpha-receptors in the greater curvature of the stomach; by alpha- and beta-receptors in the duodenum and jejunum; 2) receptors in the large intestine are of another alpha-adrenergic type than those in the small intestines. Evidence was provided for a gradient of diminishing vasodilating effects of adrenaline from cranial to caudal of the gut.


Absent stapedial reflex: otosclerosis or middle ear tumor?
We present an unusual case in which a patient diagnosed as having otosclerosis on the basis of clinical and audiologic findings actually had a middle ear facial nerve schwannoma. To the best of our knowledge, this is the first reported case in English literature in which a facial nerve schwannoma presented with conductive deafness of gradual onset and absent stapedial reflex with a normally functioning facial nerve. We also include a review of the literature.


The perceived control model of falling: developing a unified framework to understand and assess maladaptive fear of falling.
fear of falling is common in older adults and can have a profound influence on a variety of behaviours that increase fall risk. However, fear of falling can also have potentially positive outcomes for certain individuals. Without progressing our understanding of mechanisms underlying these contrasting outcomes, it is difficult to clinically manage fear of falling. this paper first summarises recent findings on the topic of fear of falling, balance and fall risk-including work highlighting the protective effects of fear. Specific focus is placed on describing how fear of falling influences perceptual, cognitive and motor process in ways that might either increase or reduce fall risk. Finally, it reports the development and validation of a new clinical tool that can be used to assess the maladaptive components of fear of falling. we present a new conceptual framework-the Perceived Control Model of Falling-that describes specific mechanisms through which fear of falling can influence fall risk. The key conceptual advance is the identification of perceived control over situations that threaten one's balance as the crucial factor mediating the relationship between fear and increased fall risk. The new 4-item scale that we develop-the Updated Perceived Control over Falling Scale (UP-COF)-is a valid and reliable tool to clinically assess perceived control. this new conceptualisation and tool (UP-COF) allows clinicians to identify individuals for whom fear of falling is likely to increase fall risk, and target specific underlying maladaptive processes such as low perceived control.


Coulomb scattering in a 2D interacting electron gas and production of EPR pairs.
We propose a setup to generate nonlocal spin Einstein-Podolsky-Rosen pairs via pair collisions in a 2D interacting electron gas, based on constructive two-particle interference in the spin-singlet channel at the pi/2 scattering angle. We calculate the scattering amplitude via the Bethe-Salpeter equation in the ladder approximation and small r(s) limit and find that the Fermi sea leads to a substantial renormalization of the bare scattering process. From the scattering length, we estimate the current of spin-entangled electrons and show that it is within experimental reach.


A Multivariate Evaluation of Factors Affecting the Quality of Freshly Frozen Tissue Specimens.
Well-prepared and preserved freshly frozen specimens are indispensable materials for clinical studies. To manage specimen quality and to understand the factors potentially affecting specimen quality during preservation processes, we analyzed the quality of RNA and genomic DNA of various tissues collected between 2002 and 2011 in Linkou Chang Gung Memorial Hospital, Taiwan. During this period, a total of 1059 freshly frozen specimens from eight major cancer categories were examined. It was found that preservation duration, organ origin, and tissue type could all influence the quality of RNA samples. The increased preservation period correlated with decreased RNA quality; the brain, breast, and stomach RNA specimens displayed faster degradation rates than those of other organs, and RNA specimens isolated from tumor tissues were apparently more stable than those of other tissues. These factors could all be used as quality predictors of RNA quality. In contrast, almost all analyses revealed that the genomic DNA samples had good quality, which was not influenced by the aforementioned factors. The results assisted us in determining preservation factors that affect specimen quality, which could provide evidence for improving processes of sample collection and preservation. Furthermore, the results are also useful for researchers to adopt as the evaluation criteria for choosing specimen collection and preservation strategies.


A Customizable Chamber for Measuring Cell Migration.
Cell migration is a vital part of immune responses, growth, and wound healing. Cell migration is a complex process that involves interactions between cells, the extracellular matrix, and soluble and non-soluble chemical factors (e.g., chemoattractants). Standard methods for measuring the migration of cells, such as the Boyden chamber assay, work by counting cells on either side of a divider. These techniques are easy to use; however, they offer little geometric modification for different applications. In contrast, microfluidic devices can be used to observe cell migration with customizable concentration gradients of soluble factors1,2. However, methods for making microfluidics based assays can be difficult to learn. Here, we describe an easy method for creating cell culture chambers to measure cell migration in response to chemical concentration gradients. Our cell migration chamber method can create different linear concentration gradients in order to study cell migration for a variety of applications. This method is relatively easy to use and is typically performed by undergraduate students. The microchannel chamber was created by placing an acrylic insert in the shape of the final microchannel chamber well into a Petri dish. After this, poly(dimethylsiloxane) (PDMS) was poured on top of the insert. The PDMS was allowed to harden and then the insert was removed. This allowed for the creation of wells in any desired shape or size. Cells may be subsequently added to the microchannel chamber, and soluble agents can be added to one of the wells by soaking an agarose block in the desired agent. The agarose block is added to one of the wells, and time-lapse images can be taken of the microchannel chamber in order to quantify cell migration. Variations to this method can be made for a given application, making this method highly customizable.


The culture of 12- and 13-day rat embryos using continuous and noncontinuous gassing of rotating bottles.
A technique for the culture of 12- and 13-day rat embryos is presented. The culture method described utilizes the opening of the extraembryonic membranes together with a simple bottle rotator during incubation to facilitate tissue oxygenation. This method was compared with a more elaborate device that enabled constant gassing during incubation. Best results were obtained with 12-day embryos cultured for 24 hr in closed bottles. Thereafter, there was a marked falloff in embryonic development in culture. Optimal medium conditions were 25% rat serum in tissue culture medium with a gas phase of 60% O2, 5% CO2, 35% N2. The culture method described allows for larger numbers of embryos to be cultured more simply than previous methods and should be valuable to workers wishing to study embryos in the more advanced stages of organogenesis.


Improved exercise performance following lung volume reduction surgery for emphysema.
Lung volume reduction surgery (LVRS) for emphysema has been suggested to improve patient lung function and activity. The short-term impact of LVRS on exercise performance was evaluated using maximal and submaximal steady-state exercise testing in 27 patients with severe hypoxemic chronic obstructive pulmonary disease (COPD), along with measurements of patient function, dyspnea, and quality of life. LVRS significantly improved exercise performance, due to ventilatory improvements associated with increased ventilatory reserve, enhanced tidal volume recruitment, and improved alveolar ventilation. Preoperative measurements of ventilatory reserve and dead space ventilation during exercise testing were closely associated with improved exercise performance. Improvements in patient dyspnea, walk distances, and quality of life also occurred following LVRS and were associated with improvements in exercise performance. Surgical mortality from LVRS was low (4%), but short-term all-cause mortality was increased (19%). Short-term mortality was associated with reduced expiratory muscle strength and markedly elevated dead space ventilation. We conclude that LVRS produces significant improvements in exercise performance, dyspnea, and quality of life in selected patients with COPD. Physiologic prediction of patients most likely to survive for an extended period and have significant benefit following LVRS may also be possible.


MVPA-Light: A Classification and Regression Toolbox for Multi-Dimensional Data.
MVPA-Light is a MATLAB toolbox for multivariate pattern analysis (MVPA). It provides native implementations of a range of classifiers and regression models, using modern optimization algorithms. High-level functions allow for the multivariate analysis of multi-dimensional data, including generalization (e.g., time x time) and searchlight analysis. The toolbox performs cross-validation, hyperparameter tuning, and nested preprocessing. It computes various classification and regression metrics and establishes their statistical significance, is modular and easily extendable. Furthermore, it offers interfaces for LIBSVM and LIBLINEAR as well as an integration into the FieldTrip neuroimaging toolbox. After introducing MVPA-Light, example analyses of MEG and fMRI datasets, and benchmarking results on the classifiers and regression models are presented.


The plant detectives: innovative undergraduate teaching to inspire the next generation of plant biologists.
Encouraging more students to embrace plant science research is a global priority. We have evolved a second year undergraduate course from a standard lecture/practical format into an innovative research-led learning design that gives students hands-on experience of cutting-edge plant science research and specialist instrumentation. By making tangible the links between plant genetics, biochemistry, physiology and function, the active learning curriculum extends students to their limits, and gives them insights into the multi-faceted nature of plant science research. Using genetically-mapped mutants of Arabidopsis thaliana, we challenge our students to apply their conceptual learning immediately to identify "unknown" genetic mutations affecting plant form and function. By exposing students early in their student careers to the challenges, rigors and excitement of plant science research, we have helped them grow quickly into astute researchers who truly deserve the title "Plant Detectives." Many have become motivated to continue their studies as plant biologists in research-focused honors (pre-doctoral) and doctoral programs.


Specific inhibition of the incorporation of tritiated thymidine in regenerating rat liver by a rat hepatocytes supernatant.
Studies on endogenous inhibitors obtained from supernatant fluids of rat hepatocytes indicated that the supernatant arrests the normal cell cycle at two points, namely, before the beginning of the S phase and at the onset of metaphase when assayed in regenerating liver cells in situ. The specificity of this (these) inhibitory substance(s) was evidenced by the finding that no inhibition of cell division was observed in situ in tongue, intestine, or kidneys of animals injected with concentrations of the hepatocyte supernatant that inhibited cell division in regenerating liver. When higher concentrations of the inhibitor-containing supernatant were used, only the tongue epithelial cells were affected in addition to the regenerating liver cells.


Prevalence of Potentially Inappropriate Medication Use in Older Adults Living in Nursing Homes: A Systematic Review.
As older adults living in nursing homes are at a high risk of adverse drug-related events, medications with a poor benefit/risk ratio or with a safer alternative should be avoided. To systematically evaluate the prevalence of potentially inappropriate medication use in nursing home residents. We searched in PubMed and EMBASE databases (1990-2015) for studies reporting the prevalence of potentially inappropriate medication use in people ≥60 years of age living in nursing homes. The risk of bias was assessed with an adapted version of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. A total of 91 articles were assessed for eligibility, and 48 met our inclusion criteria. These articles reported the findings from 43 distinct studies, of which 26 presented point prevalence estimates of potentially inappropriate medication use (227,534 nursing home residents). The overall weighted point prevalence of potentially inappropriate medication use in nursing homes was 43.2% [95% confidence interval (CI) 37.3%-49.1%], increasing from 30.3% in studies conducted during 1990-1999 to 49.8% in studies conducted after 2005 (P < .001). Point prevalence estimates reported in European countries were found to be higher (49.0%, 95% CI 42.5-55.5) than those reported in North America (26.8%, 95% CI 16.5-37.1) or in other countries (29.8%, 95% CI 19.3-40.3). In addition, 18 studies accounting for 326,562 nursing home residents presented 20 distinct period prevalence estimates ranging from 2.3% to 50.3%. The total number of prescribed medications was consistently reported as the main driving factor for potentially inappropriate medications use. This systematic review shows that almost one-half of nursing home residents are exposed to potentially inappropriate medications and suggests an increase prevalence over time. Effective interventions to optimize drug prescribing in nursing home facilities are, therefore, needed.


Optimization of two flow-injection spectrophotometric methods for the determination of indapamide in pharmaceutical dosage forms.
Multivariate experimental design has been used to optimize 2 flow-injection spectrophotometric methods for the determination of indapamide in pharmaceutical dosage forms, both pure and commercial tablets. The methods are based on the oxidation of this drug with iron (III) in acidic medium and the subsequent formation of an intensive orange-red complex between the liberated iron (II) and 2,2'-bipyridyl or 1,10-phenanthroline reagents. Plackett-Burman designs were applied as a screening method to evaluate the most significant factors with few experiments. Central composite 2(3)+ star designs were performed to evaluate the response surfaces. The methods have been fully validated and were applied successfully to the determination of indapamide in pure and pharmaceutical forms with good accuracy and precision. Therefore, the 2 proposed procedures are simple, inexpensive, and rapid flow methods for the routine determination of indapamide in pharmaceutical preparations.


Central auditory processing, MRI morphometry and brain laterality: applications to dyslexia.
We review data from our laboratory related to a view of dyslexia as a biological disorder, or deficit, caused by both structural and functional brain abnormalities. The review is focused on central auditory processing in dyslexia, and the possibility that impairments in the auditory or acoustic features of the phonological code may be at the heart of the impairments seen in dyslexia. Three methodological approaches by which to investigate central auditory processing deficits are outlined: dichotic listening (DL) to consonant-vowel syllables; magnetic resonance imaging (MRI), and the use of event-related potentials (ERPs). Consonant-vowel syllable DL is a technique for probing the functional status of phonological processing areas in the superior temporal gyrus, particularly in the left hemisphere. MRI is a corresponding structural, or morphological, measure of anatomical abnormalities in the same brain region, particularly covering the planum temporale area. The ERP technique, and particularly the mismatch negativity (MMN) component, reveals cortical dysfunctions in sensory processing and memory related to basic acoustic events. For all three approaches, the dyslexic children were seen to differ from their control counterparts, including absence of modulation of the right ear advantage (REA), in DL through shifting of attention, smaller left-sided planum temporale asymmetry, and prolonged latency in the MMN ERP complex, particularly in the time-deviant stimulus condition.


Acute hypothalamic-pituitary-adrenal responses to the stress of treadmill exercise. Physiologic adaptations to physical training.
To study the effects of physical conditioning on the hypothalamic-pituitary-adrenal axis, we examined the plasma ACTH, cortisol, and lactate responses in sedentary subjects, moderately trained runners, and highly trained runners to graded levels of treadmill exercise (50, 70, and 90 percent of maximal oxygen uptake) and to intravenous ovine corticotropin-releasing hormone (1 microgram per kilogram of body weight). Basal evening concentrations of ACTH and cortisol, but not of lactate, were elevated in highly trained runners as compared with sedentary subjects and moderately trained runners. Exercise-stimulated ACTH, cortisol, and lactate responses were similar in all groups and were proportional to the exercise intensity employed. These responses, however, were attenuated in the trained subjects when plotted against applied absolute workload. Only the highly trained group had diminished responses of ACTH and cortisol to ovine corticotropin-releasing hormone, consistent with sustained hypercortisolism. We conclude that physical conditioning is associated with a reduction in pituitary-adrenal activation in response to a given workload. Alterations of the hypothalamic-pituitary-adrenal axis consistent with mild hypercortisolism and similar to findings in depression and anorexia nervosa were found only in highly trained runners. Whether these alterations represent an adaptive change to the daily stress of strenuous exercise or a marker of a specific personality profile in highly trained athletes is unknown.


Generation of spin waves by a train of fs-laser pulses: a novel approach for tuning magnon wavelength.
Currently spin waves are considered for computation and data processing as an alternative to charge currents. Generation of spin waves by ultrashort laser pulses provides several important advances with respect to conventional approaches using microwaves. In particular, focused laser spot works as a point source for spin waves and allows for directional control of spin waves and switching between their different types. For further progress in this direction it is important to manipulate with the spectrum of the optically generated spin waves. Here we tackle this problem by launching spin waves by a sequence of femtosecond laser pulses with pulse interval much shorter than the relaxation time of the magnetization oscillations. This leads to the cumulative phenomenon and allows us to generate magnons in a specific narrow range of wavenumbers. The wavelength of spin waves can be tuned from 15 μm to hundreds of microns by sweeping the external magnetic field by only 10 Oe or by slight variation of the pulse repetition rate. Our findings expand the capabilities of the optical spin pump-probe technique and provide a new method for the spin wave generation and control.


A self-assembled 3D Pt/TiO2 architecture for high-performance photocatalytic hydrogen production.
A 3D Pt/TiO2 architecture assembled from 1D nanowires has been designed and successfully prepared by an environmentally-friendly one-pot solvothermal process. The formation mechanism has been investigated and the unique architecture exhibits an excellent photocatalytic hydrogen production rate as high as 13.33 mmol h(-1) g(-1), the corresponding apparent quantum efficiency reaches 34%.


Genetic Testing for Breast Cancer Susceptibility Should Be Offered before Unilateral Abdominally Based Free Flap Breast Reconstruction.
Pathogenic mutations have been identified in approximately 10 percent of patients who present with breast cancer. Notably, failure to identify deleterious genetic mutations has particular implications for patients undergoing abdominally based breast reconstruction, as the donor site can be used only once. The authors sought to determine: (1) how many patients underwent genetic testing before unilateral abdominally based free flap breast reconstruction; (2) how often deleterious mutations were detected after abdominally based free flap breast reconstruction; and (3) the cost-effectiveness of expanding genetic testing in this patient population. The authors retrospectively identified all patients who underwent unilateral abdominally based free flap breast reconstruction at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2007 and 2016. Chart review was performed to collect relevant demographic and clinical data. Relevant hospital financial data were obtained. Of the 713 who underwent free flap breast reconstruction, 160 patients met inclusion criteria, and mean follow-up was 5.8 years. Three patients (1.9 percent of 160) underwent contralateral surgery after completing reconstruction, two of whom had BRCA2 and one with ATM mutation. One hundred eleven patients met National Comprehensive Cancer Network guidelines for genetic testing, but of those only 55.9 percent (62 patients) were tested. Financial data revealed that testing every patient in the cohort would result in a net savings of $262,000. During a relatively short follow-up period, a small percentage of patients were diagnosed with pathogenic mutations and underwent contralateral mastectomy and reconstruction. However, because of the costliness of surgery and the decreased cost of genetic testing, it is cost-effective to test every patient before unilateral abdominally based free flap breast reconstruction.


A radiographic study estimating age of mandibular third molars by periodontal ligament visibility.
Visibility of the periodontal ligament of mandibular third molars (M3) has been suggested as a method to estimate age. To assess the accuracy of this method and compare the visibility of the periodontal ligament in the left M3 with the right M3. The sample was archived panoramic dental radiographs of 163 individuals (75 males, 88 females, age 16-53 years) with mature M3's. Reliability was assessed using Kappa. Accuracy was assessed by subtracting chronological age from estimated age for males and females. Stages were cross-tabulated against age stages younger than and at least 18 and 21 years of age. Stages were compared in the left M3 and right M3. Analysis showed excellent intra-observer reliability. Mean difference between estimated and chronological ages was 7.21 years (SD 5.16) for left M3 and 7.69 (SD 6.08) for right M3 in males and 6.87 (SD 5.83) for left M3 and 8.61 (SD 6.58) for right M3 in females. Minimum ages of stages 0 to 2 were younger than previously reported, despite a small sample of individuals younger than 18. The left and right M3 stage differed in 46% of the 85 individuals with readings from both side and estimated age differed from -10.5 to 12.2 years between left and right. Accuracy of this method was between 6 and 8 years with an error of 5 to 6 years. The number of individuals with mature M3 apices younger than 18 years was small. The stage of visibility of the periodontal ligament differed between left and right in almost half of our sample with both teeth present. Our findings question the use of this method to estimate age or to discriminate between age younger and at least 18 years.


[Sleep apnea : diagnostic and therapeutic modalities in case of failure of the CPAP].
Obstructive sleep apnea (OSA) is a sleep disorder that affects 49 % of men and 23% of women over 40 years old. CPAP is currently the treatment of choice for severe OSAS, but there are mild to moderate cases of OSAS with poor compliance or intolerance to CPAP, for which alternative treatments should be considered. In this article, we present a tool for evaluation of the upper airways, the DISE (Drug-induced sleep endoscopy), the OAM (mandibular advancement device), the bimaxillary advancement osteotomy, the hypoglossal nerve stimulation and the positional treatment.


Trajectories of risky drinking around the time of statutory retirement: a longitudinal latent class analysis.
Life transitions such as retirement may influence alcohol consumption, but only a few studies have described this using longitudinal data. We identified patterns and predictors of risky drinking around the time of retirement. A cohort study assessing trajectories and predictors of risky drinking among employees entering statutory retirement between 2000 and 2011. A total of 5805 men and women from the Finnish Public Sector study who responded to questions on alcohol consumption one to three times prior to (w-3 , w-2 , w-1 ), and one to three times after (w+1 , w+2 , w+3 ) retirement. We assessed trajectories of risky drinking (> 24 units per week among men, > 16 units among women, or an extreme drinking occasion during past year) from pre- to post-retirement, as well as predictors of each alcohol consumption trajectory. Three trajectories were identified: sustained healthy drinking (81% of participants), temporary increase in risky drinking around retirement (12%) and slowly declining risky drinking after retirement (7%). The strongest pre-retirement predictors for belonging to the group of temporary increase in risky drinking were current smoking [odds ratio (OR) = 3.90, 95% confidence interval (CI) = 2.70-5.64], male sex (OR = 2.77, 95% CI = 2.16-3.55), depression (OR = 1.44, 95% CI = 1.05-1.99) and work-place in the metropolitan area (OR = 1.29, 95% CI = 1.00-1.66). Compared with the slowly declining risky drinking group, the temporary increase in risky drinking group was characterized by lower occupational status and education, and work-place outside the metropolitan area. In Finland, approximately 12% of people who reach retirement age experience a temporary increase in alcohol consumption to risky levels, while approximately 7% experience a slow decline in risky levels of alcohol consumption. Male gender, smoking, being depressed and working in a metropolitan area are associated with increased likelihood of increased alcohol consumption.


Inhibition of phospholipase D by agents that inhibit cell growth.
The phospholipases are an important class of enzymes for growth factor and oncogene intracellular signalling. The anti-tumor drug suramin was found to inhibit phosphatidylcholine hydrolysis and trans-phosphatidylation by solubilized rat brain phospholipase D (PLD) with an IC50 of 15 microM. An azo analogue of suramin, which is a considerably more potent inhibitor of phosphatidylinositol phospholipase C (PIPLC) than suramin, inhibited PLD with and IC50 of 58 microM. D-609, a xanthogenate compound with in vitro antitumor activity, inhibited PLD with an IC50 of 820 microM. The cytotoxic aminosteroid compound U-73, 122 was a weaker inhibitor of PLD with an IC50 of 78 microM. However, U-73, 122 was a more potent inhibitor of PLD in fibroblast membranes with an IC50 of 25 microM, while suramin was less active with an IC50 of 4.2 mM. The antitumor ether lipid drug ET-18-OCH3 did not inhibit solubilized or membrane PLD although it is a potent inhibitor of PIPLC. The results of the study show that the compounds tested have different abilities to inhibit PIPLC and PLD. Access of hydrophilic drugs to membrane PLD may be a limiting factor to their inhibitory activity.


Familial early onset of type-2 diabetes mellitus and its complications.
Globally, the prevalence of chronic, non-communicable diseases is increasing at an alarming rate. Furthermore, approximately 197 million people worldwide have impaired glucose tolerance. Consequently, diabetes is rapidly emerging as a global health problem that threatens to assume a pandemic level by 2030. In Indian population, genetic predisposition to trigger diabetes at an early age as compared to western counterpart has been focused very much. To gain further insight into the positive correlation between the diabetes and family history was the objective of this study. Patients attending the Diabetes Centre, K.L.E.S Dr. Prabhakar. Kore Hospital and Medical Research Centre; J. N. Medical College; KLE University Belgaum, Karnataka- India, were recruited, diagnosed and analyzed as per WHO criteria. The prevalence of diabetes was higher among patients with diabetic mother (25.6%) compared to patients with diabetic father (21.2%) and there was early onset of type -2 diabetes among patients having both parents with diabetic when compared to other patients. Based on the present observation, it would be appropriate to emphasize again that a strong family history for diabetes, would signal at an early age, the onset of diabetes perhaps with its complications.


Cultural teaching: the development of teaching skills in Maya sibling interactions.
Psychology has considered the development of learning, but the development of teaching in childhood has not been considered. The data presented in this article demonstrate that children develop teaching skills over the course of middle childhood. Seventy-two Maya children (25 boys, 47 girls) ranging in age from 3 to 11 years (M = 6.8 years) were videotaped in sibling caretaking interactions with their 2-year-old brothers and sisters (18 boys, 18 girls). In the context of play, older siblings taught their younger siblings how to do everyday tasks such as washing and cooking. Ethnographic observations, discourse analyses, and quantification of discourse findings showed that children's teaching skills increased over the course of middle childhood. By the age of 4 years, children took responsibility for initiating teaching situations with their toddler siblings. By the age of 8 years, children were highly skilled in using talk combined with manual demonstrations, verbal feedback, explanations, and guiding the body of younger learners. Children's developing competence in teaching helped their younger siblings increase their participation in culturally important tasks.


RhoA/Rho-kinase and nitric oxide in vascular reactivity in rats with endotoxaemia.
RhoA/Rho-kinase (RhoA/ROK) pathway promotes vasoconstriction by calcium sensitivity mechanism. LPS causes nitric oxide (NO) overproduction to induce vascular hyporeactivity. Thus, we tried to examine the role of RhoA/ROK and NO in the regulation of vascular reactivity in different time-point of endotoxaemia. Male Wistar rats were intravenously infused for 10 min with saline or E. coli endotoxin (lipopolysaccharide, LPS, 10 mg/kg) and divided to five groups (n = 8 in each group): (i) Control, sacrificed at 6 h after saline infusion; (ii) LPS1h, sacrificed at 1 h after LPS infusion; (iii) LPS2h, sacrificed at 2 h after LPS infusion; (iv) LPS4h, sacrificed at 4 h after LPS infusion; and (v) LPS6h, sacrificed at 6 h after LPS infusion. LPS1h and LPS2h were regarded as early endotoxaemia, whereas LPS4h and LPS6h were regarded as late endotoxaemia. Indeed, our results showed that LPS reproduced a biphasic hypotension and sustained vascular hyporeactivity to noradrenaline (NA) in vivo. Interestingly, this hyporeactivity did not occur in ex vivo during early endotoxaemia. This could be due to increases of aortic RhoA activity (n = 5, P<0.05) and myosin phosphatase targeting subunit 1 phosphorylation (n = 3, P<0.05). In addition, pressor response to NA and vascular reactivity in early endotoxaemia were inhibited by ROK inhibitor, Y27632. Furthermore, plasma bradykinin was increased at 10 min (24.6±13.7 ng/mL, n = 5, P<0.05) and aortic endothelial NO synthase expression was increased at 1 h (+200%. n = 3, P<0.05) after LPS. In late endotoxaemia, the vascular hyporeactivity was associated with aortic inducible NO synthase expression (n = 3, P<0.05) and an increased serum NO level (n = 8, P<0.05). Thus, an increased RhoA activity could compensate vascular hyporeactivity in early endotoxaemia, and the large NO production inhibiting RhoA activity would lead to vascular hyporeactivity eventually.


Somatic versus nonsomatic shoulder and back pain experience in middle age in relation to body build, physical fitness, bone mineral content, gamma-glutamyltransferase, occupational workload, and psychosocial factors.
This study selected 205 subjects aged 55 years who had shoulder and/or back pain complaints to determine the relationship of somatic and nonsomatic pain experience to body build, physical fitness, bone mineral content, serum levels of gamma-glutamyltransferase, occupational workload and intelligence test, educational level, life success, social support, stress at work, monotonous work, and job decision latitude. Men with a somatic back pain drawing experienced more stress at work and had higher serum levels of gamma-glutamyltransferase, indicating a higher intake of alcohol and/or painkillers, but were more satisfied with their jobs compared with men who had a nonsomatic pain drawing. Women with obvious shoulder signs and symptoms and/or a somatic back pain drawing tended heavier than women without symptoms, had higher serum levels of gamma-glutamyltransferase, and found their jobs more mentally demanding than did women with shoulder and/or back pain experience but without obvious shoulder signs and symptoms and/or a nonsomatic back pain drawing.


Negative effective mass of wave-driven classical particles in dielectric media.
For a classical particle undergoing nonlinear interaction with a wave in dielectric medium, a perturbation theory is developed, showing that the particle motion can be described in terms of an effective parallel mass which can become negative. A relativistic particle interacting with a circularly polarized wave and a static magnetic field is studied as an example. For the three stationary orbits corresponding to the same velocity parallel to the magnetic field, the conditions are found under which all these equilibria are centerlike, or neutrally stable. It is shown that a negative parallel mass is realized in the vicinity of the intermediate-energy equilibrium and can lead to a plasma collective instability.


Hospitalisation rates for children with intellectual disability or autism born in Western Australia 1983-1999: a population-based cohort study.
To describe the hospitalisation patterns in children with intellectual disability (ID) and/or autism spectrum disorder (ASD) after the first year of life and compare with those unaffected. Prospective cohort study using data linkage between health, ID and hospitalisation population-based datasets. Western Australia. 416 611 individuals born between 1983 and 1999 involving 1 027 962 hospital admission records. Five case categories were defined (mild/moderate ID, severe ID, biomedically caused ID, ASD with ID and ASD without ID) and compared with the remainder of children and young people. Time to event analysis was used to compare time hospitalisation and rate of hospitalisation between the different case-groups by estimating HR, accounting for birth year and preterm birth status. ID and/or ASD were found to be associated with an increased risk of hospitalisation compared with the remainder of the population. The increase in risk was highest in those with severe ID and no ASD (HR=10.33, 95% CI 8.66 to 12.31). For those with ID of known biomedical cause or mild ID of unknown cause, the risk of hospitalisation was lower (HR=7.36, 95% CI 6.73 to 8.07 and HR=3.08, 95% CI 2.78 to 3.40, respectively). Those with ASDs had slightly increased risk (HR=2.82, 95% CI 2.26 to 3.50 for those with ID and HR=2.09, 95% CI 1.85 to 2.36 for those without ID). Children with an ID or ASD experience an increased risk of hospitalisation after the first year of life which varied from 2 to 10 times that of the rest of the population. Findings can inform service planning or resource allocation for these children with special needs.


Serotonergic neurons are involved in the counter-regulatory response to hypoglycemia.
Intensive insulin therapy provides optimal glycemic control in patients with diabetes. However, intensive insulin therapy causes so-called iatrogenic hypoglycemia as a major adverse effect. The ventromedial hypothalamus (VMH) has been described as the primary brain area initiating the counter-regulatory response (CRR). Nevertheless, the VMH receives projections from other brain areas which could participate in the regulation of the CRR. In particular, studies suggest a potential role of the serotonin (5-HT) network. Thus, the objective of this study was to determine the contribution of 5-HT neurons in CRR control. Complementary approaches have been used to test this hypothesis in quantifying the level of 5-HT in several brain areas by HPLC in response to insulin-induced hypoglycemia, measuring the electrical activity of dorsal raphe (DR) 5-HT neurons in response to insulin or decreased glucose level by patch-clamp electrophysiology; and measuring the CRR hormone glucagon as an index of the CRR to the modulation of the activity of 5-HT neurons using pharmacological or pharmacogenetic approaches. HPLC measurements show that the 5HIAA/5HT ratio is increased in several brain regions including the VMH in response to insulin-induced hypoglycemia. Patch-clamp electrophysiological recordings show that insulin, but not decreased glucose level, increases the firing frequency of DR 5-HT neurons in the DR. In vivo, both the pharmacological inhibition of 5-HT neurons by intraperitoneal injection of the 5-HT1A receptor agonist 8-OH-DPAT or the chemogenetic inhibition of these neurons reduce glucagon secretion, suggesting an impaired CRR. Taken together, these data highlight a new neuronal network involved in the regulation of the CRR. In particular, this study shows that DR 5-HT neurons detect iatrogenic hypoglycemia in response to the increased insulin level and may play an important role in the regulation of CRR.


[Rate of retention and related factors on patients under methadone maintenance treatment in Beijing: a prospective cohort study].
To study the rates of retention and associated factors on patients under methadone maintenance treatment (MMT) in Beijing. A prospective cohort was conducted among 548 patients who enrolled in MMT clinics during 2004 - 2006 in Beijing. Log-rank method and Cox PH regression models were used to study related factors associated with long-term retention. Of the 548 patients, 463 (79.6%) were males, with 515 (94.0%) under Han ethnicity. 443 (80.8%) of them were unemployed with 449 (81.9%) as injecting drug users at the time of enrollment. The average age and duration of drug abuse at enrollment were 37.3 ± 6.7 and 9.1 ± 4.0 years, respectively. The median length of treatment was 2.1 years with five-year retention rate as 41.2%. The long-term retention rates between different dosages (Log-rank χ(2) = 10.527, P = 0.005), treatment ratio (Log-rank χ(2) = 19.027, P < 0.001) and illicit drug use (Log-rank χ(2) = 159.485, P < 0.001) showed significant differences, statistically. Factors as having high education level (HR = 0.76, P = 0.021), with daily dosage 60 mg/day or more (HR = 0.64, P = 0.002), having 1% - 9% times urine morphine positive result (HR = 0.32, P < 0.001) seemed to be able to predict the lower risk of dropout during the follow-up period. However, frequent illicit drug use (> 20%) (HR = 2.92, P < 0.001) could increase the risk of dropout. Treatment with higher dosage (≥ 60 mg/day) of methadone seemed to have decreased the possibility of dropout during the follow-up period, whereas frequent illicit drug use (≥ 20%) was important risk factor causing long-term retention.


Closing the Loop: Using Evidence to Inform Refinements to an Admissions Process.
Substantive changes in our evaluation of applicants have been implemented in response to the findings of the various phases of outcomes assessment. This article will describe the changes that have been implemented as a result of analyzing the association of pre-veterinary academic, subjective, and behavioral-event interview scores with veterinary students' performance in the DVM program, including clinical competencies, and their performance on the North American Veterinary Licensing Examination. Pre-veterinary academic performance predicted academic performance in veterinary school. Subjective measures did not, and we have reduced the faculty workload associated with that part of the evaluation of applicants. Interview scores provide additional but small value in predicting performance on clinical competencies.


Baseline clinical characteristics of predicted structural and pain progressors in the IMI-APPROACH knee OA cohort.
To describe the relations between baseline clinical characteristics of the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (IMI-APPROACH) participants and their predicted probabilities for knee osteoarthritis (OA) structural (S) progression and/or pain (P) progression. Baseline clinical characteristics of the IMI-APPROACH participants were used for this study. Radiographs were evaluated according to Kellgren and Lawrence (K&L grade) and Knee Image Digital Analysis. Knee Injury and Osteoarthritis Outcome Score (KOOS) and Numeric Rating Scale (NRS) were used to evaluate pain. Predicted progression scores for each individual were determined using machine learning models. Pearson correlation coefficients were used to evaluate correlations between scores for predicted progression and baseline characteristics. T-tests and χ2 tests were used to evaluate differences between participants with high versus low progression scores. Participants with high S progressions score were found to have statistically significantly less structural damage compared with participants with low S progression scores (minimum Joint Space Width, minJSW 3.56 mm vs 1.63 mm; p<0.001, K&L grade; p=0.028). Participants with high P progression scores had statistically significantly more pain compared with participants with low P progression scores (KOOS pain 51.71 vs 82.11; p<0.001, NRS pain 6.7 vs 2.4; p<0.001). The baseline minJSW of the IMI-APPROACH participants contradicts the idea that the (predicted) course of knee OA follows a pattern of inertia, where patients who have progressed previously are more likely to display further progression. In contrast, for pain progressors the pattern of inertia seems valid, since participants with high P score already have more pain at baseline compared with participants with a low P score.